IRCCS, San Raffaele Pisana Hospital, Department of Pulmonary Rehabilitation , Rome , Italy.
Expert Opin Drug Discov. 2014 Jun;9(6):595-607. doi: 10.1517/17460441.2014.909403. Epub 2014 Apr 22.
Inhaled corticosteroid anti-inflammatory therapy is effective at controlling disease symptoms of asthma, but a subset of patients remains symptomatic despite optimal treatment, creating a clear unmet medical need. Moreover, none of the currently available drugs for asthma are really disease-modifying or curative. Although murine models of asthma, based on transgenic and knockout animals, may offer an integrated pathophysiological system for studying the characteristics of airway inflammation and hyperresponsiveness, these alterations are noteworthily different compared with those observed in asthmatic patients. Since a clear functional and inflammatory relationship between the nasal mucosa and bronchial tissue in patients suffering from asthma and allergic rhinitis has been recognized, using preclinical models based on human nasal cells sampling might support a prompt and effective anti-inflammatory drug discovery in asthma.
The authors provide a review, which discusses the potential role of nasal cell sampling and its application in advanced drug discovery for asthma. The contents range from the similarities and differences between asthma and allergic rhinitis up to artificial airway models based on sophisticated human lung-on-a-chip devices.
Nasal cell sampling and processing have reached a great potential in asthma drug discovery. The authors believe that models of asthma, which are based on human nasal cells, can provide valuable indications of proof of pharmacological and potential therapeutic efficacy in both preclinical and early clinical settings.
吸入皮质类固醇抗炎疗法可有效控制哮喘的疾病症状,但仍有一部分患者即使接受最佳治疗仍存在症状,这表明存在明确的未满足的医疗需求。此外,目前用于哮喘的药物均不能真正地改变疾病进程或根治疾病。虽然基于转基因和基因敲除动物的哮喘小鼠模型可能为研究气道炎症和高反应性的特征提供一个综合的病理生理学系统,但这些改变与哮喘患者观察到的改变明显不同。由于已经认识到哮喘和变应性鼻炎患者的鼻黏膜和支气管组织之间存在明确的功能和炎症关系,因此使用基于人类鼻细胞采样的临床前模型可能有助于快速有效地发现哮喘的抗炎药物。
作者对鼻细胞采样及其在哮喘药物研发中的应用进行了综述,内容涉及哮喘和变应性鼻炎的异同,以及基于复杂的人肺芯片设备的人工气道模型。
鼻细胞采样和处理在哮喘药物发现方面具有巨大潜力。作者认为,基于人鼻细胞的哮喘模型可以在临床前和早期临床环境中提供有价值的药理学和潜在治疗疗效的证据。